Abstract

The present studies were undertaken to assess the mechanisms responsible for growth hormone-induced insulin resistance in
man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose utilization
and their relationship to monocyte insulin binding were determined in six normal volunteers after 12-h infusion of growth
hormone and 12-h infusion of saline. The infusion of growth hormone (2 μg · kg−1 · h−1) increased plasma growth hormone nearly threefold (to ≃9 ng/ml) within the range observed during sleep and exercise. This
increased plasma insulin (14 ± 1 versus 8 ± 1 μU/ml, P < 0.005) concentrations without significantly altering plasma glucose
concentrations or basal rates of glucose production and utilization. Insulin dose-response curves for both suppression of
glucose production (half-maximal response at 37 ± 3 versus 20 ± 3 μu/ml, P < 0.01) and stimulation of glucose utilization
(half-maximal response at 98 ± 8 versus 52 ± 8 μU/ml, P / 0.01) were shifted to the right with preservation of normal maximal
responses to insulin. Monocyte insulin binding was unaffected. Thus, except at near maximal insulin receptor occupancy, the
action of insulin on glucose production and utilization per number of monocyte insulin receptors occupied was decreased. These
results indicate that increases in plasma growth hormone within the physiologic range can cause insulin resistance in man,
which is due to decreases in both hepatic and extrahepatic effects of insulin. Assuming that insulin binding to monocytes
reflects insulin binding in insulin sensitive tissues, this decrease in insulin action can be explained on the basis of a
postreceptor defect.